Limited variation between SARS-CoV-2-infected individuals in domain specificity and relative potency of the antibody response against the spike glycoprotein

作者：Hanora Van Ert, Dana Bohan, Kai J. Rogers, Mohammad Fili, Roberth Anthony Rojas Chávez, Enya Qing, Changze Han, Spencer Dempewolf, Guiping Hu, Nathan Schwery, Kristina Sevcik, Natalie Ruggio, Devlin Boyt, Michael Pentella, Tom Gallagher, J. Brooks Jackson, Anna E. Merrill, C. Michael Knudson, Grant Brown, Wendy Maury, Hillel Haim · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2021 · DOI：10.1101/2021.08.04.455181 · 研究领域：SARS-CoV-2 and COVID-19 Research、SARS-CoV-2 detection and testing、COVID-19 Clinical Research Studies

ABSTRACT The spike protein of SARS-CoV-2 is arranged as a trimer on the virus surface, composed of three S1 and three S2 subunits. Infected and vaccinated individuals generate antibodies against spike, which can neutralize the virus. Most antibodies target the receptor-binding domain (RBD) and N-terminal domain (NTD) of S1; however, antibodies against other regions of spike have also been isolated. The variation between infected individuals in domain specificity of the antibodies and in their relative neutralization efficacy is still poorly characterized. To this end, we tested serum and plasma samples from 85 COVID-19 convalescent subjects using 7 immunoassays that employ different domains, subunits and oligomeric forms of spike to capture the antibodies. Samples were also tested for their neutralization of pseudovirus containing SARS-CoV-2 spike and of replication-competent SARS-CoV-2. We observed strong correlations between the levels of NTD- and RBD-specific antibodies, with a fixed ratio of each type to all anti-spike antibodies. The relative potency of the response (defined as the measured neutralization efficacy relative to the total level of spike-targeting antibodies) also exhibited limited variation between subjects, and was not associated with the overall amount of anti-spike antibodies produced. Accordingly, the ability of immunoassays that use RBD, NTD and different forms of S1 or S1/S2 as capture antigens to estimate the neutralizing efficacy of convalescent sam...